Detection of Exhaled Volatile Organic Compounds as Noninvasive Biomarkers for Pancreatic Adenocarcinoma

Exhaled volatile organic compounds (VOC) have shown promise as noninvasive biomarkers in lung cancer and pulmonary diseases. This study aimed to evaluate the role of VOC as a noninvasive biomarker for pancreatic adenocarcinoma (PDAC) and explore whether elevated VOC levels correlate with clinical characteristics such as tumor size and cancer antigen (CA)19-9 levels.

A total of 25 patients with PDAC and 23 matched control subjects were enrolled. Exhaled breath was collected and analyzed using a silicon microreactor and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Univariate analyses, Spearman correlations, and penalized regression (SCAD), along with area under the receiver-operating characteristic (ROC) curves (AUC) identified the top VOC biomarkers. VOC concentrations exceeding the 75th percentile of controls were deemed elevated with subgroup analysis comparing patients with all three elevated VOC to those without.

Five VOC (heptanone, hexanal, hexanone, malondialdehyde (MDA), and acetaldehyde) were consistently and significantly higher in patients with PDAC. The penalized regression and linear discriminant analysis (LDA) identified three top VOC (acetaldehyde, MDA, hexanone) that distinguished PDAC from controls with an AUC of 0.81. Patients exhibiting elevated levels of all three compounds had smaller tumors and lower CA19-9 levels (p < 0.05).

A distinctive profile of elevated exhaled VOC, particularly hexanone, acetaldehyde, and MDA, is associated with PDAC. These findings suggest that VOC analysis could be a novel, noninvasive method for early detection of pancreatic cancer. Further studies in larger cohorts are warranted to validate these results.